Publications by authors named "Astrid Petersmann"

62 Publications

Relative Efficacy of Different Strategies for Inhibition of in Vitro Glycolysis.

Clin Chem 2021 Jul;67(7):1032-1034

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

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http://dx.doi.org/10.1093/clinchem/hvab071DOI Listing
July 2021

Variability of Thyroid Measurements from Ultrasound and Laboratory in a Repeated Measurements Study.

Eur Thyroid J 2021 Apr 5;10(2):140-149. Epub 2020 May 5.

Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

Background: Variability of measurements in medical research can be due to different sources. Quantification of measurement errors facilitates probabilistic sensitivity analyses in future research to minimize potential bias in epidemiological studies. We aimed to investigate the variation of thyroid-related outcomes derived from ultrasound (US) and laboratory analyses in a repeated measurements study.

Subjects And Methods: Twenty-five volunteers (13 females, 12 males) aged 22-70 years were examined once a month over 1 year. US measurements included thyroid volume, goiter, and thyroid nodules. Laboratory measurements included urinary iodine concentrations and serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroglobulin. Variations in continuous thyroid markers were assessed as coefficient of variation (CV) defined as mean of the individual CVs with bootstrapped confidence intervals and as intraclass correlation coefficients (ICCs). Variations in dichotomous thyroid markers were assessed by Cohen's kappa.

Results: CV was highest for urinary iodine concentrations (56.9%), followed by TSH (27.2%), thyroglobulin (18.2%), thyroid volume (10.5%), fT3 (8.1%), and fT4 (6.3%). The ICC was lowest for urinary iodine concentrations (0.42), followed by fT3 (0.55), TSH (0.64), fT4 (0.72), thyroid volume (0.87), and thyroglobulin (0.90). Cohen's kappa values for the presence of goiter or thyroid nodules were 0.64 and 0.70, respectively.

Conclusion: Our study provides measures of variation for thyroid outcomes, which can be used for probabilistic sensitivity analyses of epidemiological data. The low intraindividual variation of serum thyroglobulin in comparison to urinary iodine concentrations emphasizes the potential of thyroglobulin as marker for the iodine status of populations.
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http://dx.doi.org/10.1159/000507018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077478PMC
April 2021

Kappa Free Light Chains in the Context of Blood Contamination, and Other IgA- and IgM-Related Cerebrospinal Fluid Disease Pattern.

Cells 2021 03 11;10(3). Epub 2021 Mar 11.

Department of Neurology, University Medicine Greifswald, 17475 Greifswald, Germany.

In this retrospective, monocentric cohort study, we tested if an intrathecal free light chain kappa (FLC-k) synthesis reflects not only an IgG but also IgA and IgM synthesis. We also analysed if FLC-k can help to distinguish between an inflammatory process and a blood contamination of cerebrospinal fluid (CSF). A total of 296 patient samples were identified and acquired from patients of the department of Neurology, University Medicine Greifswald (Germany). FLC-k were analysed in paired CSF and serum samples using the Siemens FLC-k kit. To determine an intrathecal FLC-k and immunoglobulin (Ig) A/-M-synthesis we analysed CSF/serum quotients in quotient diagrams, according to Reiber et al. Patient samples were grouped into three cohorts: cohort I ( = 41), intrathecal IgA and/or IgM synthesis; cohort II ( = 16), artificial blood contamination; and the control group ( = 239), no intrathecal immunoglobulin synthesis. None of the samples had intrathecal IgG synthesis, as evaluated with quotient diagrams or oligoclonal band analysis. In cohort I, 98% of patient samples presented an intrathecal synthesis of FLC-k. In cohort II, all patients lacked intrathecal FLC-k synthesis. In the control group, 6.5% presented an intrathecal synthesis of FLC-k. The data support the concept that an intrathecal FLC-k synthesis is independent of the antibody class produced. In patients with an artificial intrathecal Ig synthesis due to blood contamination, FLC-k synthesis is lacking. Thus, additional determination of FLC-k in quotient diagrams helps to discriminate an inflammatory process from a blood contamination of CSF.
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http://dx.doi.org/10.3390/cells10030616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998777PMC
March 2021

Disregarded Measurement Uncertainty Contributions and Their Magnitude in Measuring Plasma Glucose.

J Diabetes Sci Technol 2020 Nov 20:1932296820966353. Epub 2020 Nov 20.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Background: Each measurement is subject to measurement uncertainty (MU). Consequently, each measurement of plasma glucose concentration used for diagnosis and monitoring of diabetes mellitus (DM) is affected. Although concepts and methods of MU are well established in many fields of science and technology, they are presently only incompletely implemented by medical laboratories, neglecting MU of target values of internal quality control (IQC) materials.

Methods: An empirical and practical approach for the estimation of MU based on the analysis of routine IQC using control samples with assigned target values is presented. Its feasibility is demonstrated exemplarily by analyzing IQC data from one year obtained for glucose employing the hexokinase method with IQC of two different concentrations.

Results: Combined relative extended ( = 2) MU comprising bias, coefficient of variation (CV), and MU of the target values assigned to control materials were about 9% with a lower (~ 56 mg/dL; ~3.1 mmol/L) and 8% with a higher (~ 346 mg/dL; ~19.2 mmol/L) concentration sample, analyzing IQC of one year from three different devices.

Conclusions: Estimation of MU in this study is quite reliable due to the large number of IQC data from one year. The MU of the target values of the commercial control material in this study was considerably larger than other MU contributions, ie, standard deviation and bias. In the future, the contribution of MU of commercial IQC should be addressed more carefully and technologies to measure glucose should be geared toward smaller MU possible, as needed, especially for glucose concentration measurements in diagnosis and management of DM.
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http://dx.doi.org/10.1177/1932296820966353DOI Listing
November 2020

Auricular stimulation vs. expressive writing for exam anxiety in medical students - A randomized crossover investigation.

PLoS One 2020 27;15(8):e0238307. Epub 2020 Aug 27.

Department of Anesthesiology, University Medicine of Greifswald, Greifswald, Germany.

Objective: Auricular stimulation (AS) is a promising method in the treatment of situational anxiety. Expressive writing (EW) is an established psychological method, which reduces test anxiety and improves exam results. The aim of this crossover trial was to compare AS with EW, and with the no intervention (NI) condition, for treatment of exam anxiety.

Methods: Healthy medical students underwent 3 comparable anatomy exams with an interval of one month, either performing EW, receiving AS or NI prior to the exam; the order of interventions was randomized. AS was applied using indwelling fixed needles bilaterally at the areas innervated mostly by the auricular branch of the vagal nerve on the day before the exam. Anxiety level, measured using State-Trait-Anxiety Inventory (STAI) before and after the interventions and immediately before exam, was the primary outcome. Quality of night sleep, blood pressure, heart rate and activity of salivary alpha-amylase (sAA) were analyzed across 3 conditions.

Results: All 37 included participants completed the study. Anxiety level (STAI) decreased immediately after AS in comparison with baseline (P = 0.02) and remained lower in comparison with that after EW and NI (P<0.01) on the day of exam. After EW and NI anxiety increased on the day of exam in comparison with baseline (P<0.01). Quality of sleep improved after AS in comparison with both control conditions (P<0.01). The activity of sAA decreased after EW and after AS (P<0.05) but not after NI condition.

Conclusion: Auricular stimulation, but not expressive writing, reduced exam anxiety and improved quality of sleep in medical students. These changes might be due to reduced activity of the sympathetic nervous system.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238307PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451547PMC
October 2020

Is the Obesity Paradox in Type 2 Diabetes Due to Artefacts of Biases? An Analysis of Pooled Cohort Data from the Heinz Nixdorf Recall Study and the Study of Health in Pomerania.

Diabetes Metab Syndr Obes 2020 16;13:1989-2000. Epub 2020 Jun 16.

Department of Study of Health in Pomerania/Clinical-Epidemiological Research, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

Aims/hypothesis: There is controversy on whether an obesity paradox exists in type 2 diabetes, ie, that mortality is lowest in overweight or obesity. We examined the role of potential biases in the obesity paradox.

Methods: From two regional population-based German cohort studies - the Heinz Nixdorf Recall Study and the Study of Health in Pomerania (baseline examinations 2000-2003/1997-2001) - 1187 persons with diabetes at baseline were included (mean age 62.6 years, 60.9% males). Diabetes was ascertained by self-report of physician's diagnosis, antidiabetic medication, fasting/random glucose or haemoglobin A1c. Mortality data were assessed for up to 17.7 years. We used restricted cubic splines and Cox regression models to assess associations between body mass index (BMI) and mortality. Sensitivity analyses addressed, inter alia, exclusion of early death cases, of persons with cancer, kidney disease or with history of cardiovascular diseases, and of ever smokers. Furthermore, we examined the role of treatment bias and collider bias for the obesity paradox.

Results: In spline models, mortality risk was lowest for BMI at about 31 kg/m. Sensitivity analyses carried out one after another had hardly any impact on this result. In our cohort, persons with diabetes and BMI ≥30 kg/m did not have better treatment than non-obese patients, and we found that collider bias played only a minor role in the obesity paradox.

Conclusion: In a cohort of 1187 persons with diabetes, mortality risk was lowest in persons with moderate obesity. We cannot explain this result by a variety of sensitivity analyses.
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http://dx.doi.org/10.2147/DMSO.S242553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305936PMC
June 2020

Free light chain kappa and the polyspecific immune response in MS and CIS - Application of the hyperbolic reference range for most reliable data interpretation.

J Neuroimmunol 2020 Jun 12;346:577287. Epub 2020 Jun 12.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address:

Objectives: Free light chain kappa (FLC-k) in cerebrospinal fluid (CSF) is involved in intrathecal immune responses and is being investigated frequently for its diagnostic sensitivity. The objective of this study was the application and interpretation of FLC-k data in quotient diagrams with a hyperbolic reference range and to confirm the superior evaluation in comparison with another proposed reference method and cut-off values. Secondly, the performance of the FLC-k quotient diagram was analyzed in respect to MS and CIS patients and in relation to the polyspecific immune response.

Materials And Methods: FLC-k was analyzed in a control cohort (n = 302) and in patients with MS/CIS (n = 98) using a nephelometric FLC-k kit. The intrathecal fraction of FLC-k based on the hyperbolic reference range was calculated in comparison to various linear FLC-k indices and routine CSF parameters [oligoclonal bands (OCB), polyspecific antiviral immune response].

Results: Using the new hyperbolic reference range, intrathecal FLC-k synthesis was found in 20 / 302 OCB negative controls. The sensitivity in the definitive MS cohort was 100%, compared to 93% positive OCB. The linear FLC-k Index interpretation with similar sensitivity for MS, however, bares the risk for the control samples,depending on the reference range, of false positive interpretations (up to 7 at low QAlb) or false negative interpretations (up to 17/20 FLC-k positives at high QAlb). The quantitative mean intrathecal FLC-k synthesis in the CIS cohort (later MS) was even slightly higher than in initially definitive MS questioning a pathophysiological difference. A positive MRZ reaction found in 53% percent of CIS patients with intrathecal FLC-k synthesis could have allowed diagnosis of MS immediately, i.e. earlier than with the Mc Donald criteria.

Conclusions: The evaluation of FLC-k with hyperbolic reference range in quotient diagrams is superior to other analytical methods like the linear FLC-k index. We suggest a sequential CSF testing with FLC-k Reibergram evaluation, potentially followed by isoelectric focusing. With the MRZ reaction we obtain highest specificity for MS diagnosis.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577287DOI Listing
June 2020

Response to Dr. Sadler's comments.

Scand J Clin Lab Invest 2020 10 29;80(6):448-449. Epub 2020 May 29.

Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1080/00365513.2020.1768589DOI Listing
October 2020

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Mol Psychiatry 2021 Jun 5;26(6):2111-2125. Epub 2020 May 5.

Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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http://dx.doi.org/10.1038/s41380-020-0719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641978PMC
June 2021

Effect of periodontal therapy on adipokine biomarkers in overweight.

J Clin Periodontol 2020 07 11;47(7):842-850. Epub 2020 May 11.

Department of Periodontology and Operative Dentistry, University Hospital Münster, Münster, Germany.

Aim: The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy.

Materials And Methods: This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m ) or moderate (21-24 kg/m ) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4.

Results: At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable.

Conclusion: Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients.
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http://dx.doi.org/10.1111/jcpe.13288DOI Listing
July 2020

Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples.

Scand J Clin Lab Invest 2020 May 23;80(3):202-209. Epub 2020 Jan 23.

Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.
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http://dx.doi.org/10.1080/00365513.2020.1716266DOI Listing
May 2020

Definition, Classification and Diagnosis of Diabetes Mellitus.

Exp Clin Endocrinol Diabetes 2019 Dec 20;127(S 01):S1-S7. Epub 2019 Dec 20.

Clinical Chemistry and Pathobiochemistry - Central Laboratory, University Hospital Tübingen, Germany.

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http://dx.doi.org/10.1055/a-1018-9078DOI Listing
December 2019

Measurement Uncertainty Impacts Diagnosis of Diabetes Mellitus: Reliable Minimal Difference of Plasma Glucose Results.

Diabetes Ther 2020 Jan 16;11(1):293-303. Epub 2019 Dec 16.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Introduction: The diagnosis of diabetes mellitus is based on suitable cut-off values of specific biomarkers, such as the concentration of glucose in plasma. The German Diabetes Association has very recently published a clinical practice guideline on the definition, classification and diagnosis of diabetes mellitus that recommends measurements of plasma glucose concentration have an imprecision defined as a minimal difference (MD) of at a fasting plasma glucose concentration of 7.0 mmol/L. To obtain reliable values for the MD, we investigated long-term and short-term measurement uncertainty.

Methods: The imprecision was determined by two approaches: (1) a long-term dataset with imprecision based on the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK), in a medical laboratory operating 24/7, using internal quality control (IQC) data for four concentrations during a 10-year period; and (2) a detailed short-term dataset with imprecision assessed by hourly measurements of control materials. These datasets were used to calculate the MD cut-off (MD) as: [Formula: see text]  = 2  [Formula: see text], where SD is the standard deviation and k = 2 represents a confidence level of 95%.

Results: The MD of ≤ 0.7 mmol/L at a fasting plasma glucose concentration of 7.0 mmol/L (MD) for the long-term and the short-term approaches were 0.44 and 0.40 mmol/L, respectively. The MD from both approaches was therefore below the recommended value of 0.7 mmol/L. It was noted that the variability in performance within and between instruments can be covered by reporting the long-term MD across all connected instruments. In this study, stable results for the MD were obtained after 1 year.

Conclusion: Imprecision as measured by IQC data is remarkably stable over many years of operation. Current imprecision assessment usually focuses on only single instruments, whereas clinicians perceive the measurement as the result of the combined analytical performance of all instruments used for a certain assay. In the clinical setting, the MD may be a more useful measure of imprecision, and we suggest deriving the MD combined from all instruments and control cycles that are used in the patient care setting for a given analyte.
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http://dx.doi.org/10.1007/s13300-019-00740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965559PMC
January 2020

Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia.

J Transl Med 2019 11 11;17(1):365. Epub 2019 Nov 11.

Research Group "Biomarkers for Infectious Diseases", TWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.

Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage.

Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls.

Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution.

Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.
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http://dx.doi.org/10.1186/s12967-019-2112-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849224PMC
November 2019

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

J Am Coll Cardiol 2019 06;73(24):3118-3131

Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.

Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.

Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.

Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.
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http://dx.doi.org/10.1016/j.jacc.2019.03.519DOI Listing
June 2019

Mean platelet volume is more important than age for defining reference intervals of platelet counts.

PLoS One 2019 14;14(3):e0213658. Epub 2019 Mar 14.

Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.

Background: Platelet count is known to be associated with sex, age and mean platelet volume (MPV). Sex and age were proposed for adjustment of platelet count reference intervals, but MPV is currently not used for further adjustment. We investigated the association of MPV, age and sex with platelet counts and established individualized reference ranges respecting MPV.

Methods: The association of platelet count with age, sex and MPV was assessed in healthy participants (n = 3,033 individuals; 1,542 women) in the cross-sectional population-based cohort Study of Health in Pomerania. Reference intervals respecting age, sex, and MPV were estimated using quantile regressions for the 2.5th and 97.5th percentile.

Results: Women had higher platelet counts than men (239 vs. 207 x109/L, p<0.001). Platelet counts correlated with age (p<0.001) and MPV (p<0.001). Quantile regression of lower and upper platelet count limits correlated less with age in female (p = 0.047 for 2.5th percentile; p = 0.906 for 97.5th percentile) and male subjects (p = 0.029 for 2.5th percentile; p = 0.195 for 97.5th percentile) compared to MPV (p<0.001 for upper and lower limit for both sexes). After adjustment for MPV, age did no longer correlate with the 2.5th (p = 0.165) or 97.5th percentile (p = 0.999) of platelet count. In contrast, after adjustment for age, MPV levels still significantly correlated with 2.5th, 50th and 97.5th percentile (p<0.001).

Conclusion: MPV and sex have a stronger association with platelet count than age. MPV should be considered to adjust platelet count reference intervals and needs to be respected as confounder for platelet counts in epidemiological studies and clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417788PMC
December 2019

Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts.

BMC Endocr Disord 2019 Feb 12;19(1):20. Epub 2019 Feb 12.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.

Background: Measurement of gylcated hemoglobin A1c (HbA1c) plays a central role in monitoring quality of antidiabetic therapy and in the diagnosis of diabetes. Several studies report increased levels of HbA1c in nondiabetic elderly. However, this observation did not reach incorporation into daily clinical practice or the respective guidelines. The present study aimed to evaluate HbA1c levels in relation to age in two independent population-based cohorts and to derive age-specific reference intervals.

Methods: Four thousand two hundred sixty three participants from the Study of Health in Pomerania (SHIP-0) and 4402 participants from the independent study SHIP-Trend were included. HbA1c was determined by means of high-performance liquid chromatography. Multivariable linear regression models were performed. Reference intervals for HbA1c were determined.

Results: Reference intervals were derived from a healthy subpopulation with the upper reference limit (URL) for HbA1c of 42.1 mmol/Mol (6.0%) for individuals aged 20-39 years increasing to 43.2 mmol/Mol (6.1%) for individuals aged 40-59 years. For people aged ≥60 years the URL was 47.5 mmol/Mol (6.5%). In both study populations an increase in HbA1c with age was observed. ANOVA revealed up to 8.5 mmol/Mol (0.77%) or 7.3 mmol/Mol (0.68%) higher estimated mean levels of HbA1c in the oldest compared to the youngest age group in SHIP-0 or SHIP-trend, respectively. Linear regression analyses confirmed the positive associations of HbA1c with age which was independent of BMI CONCLUSION: The present study confirmed the previously observed increase of HbA1c with increasing age in non-diabetic individuals. As a consequence age-dependent reference values for HbA1c were derived from two large and well defined reference populations. Implementation of them into daily practice may improve patient care and diagnosis of diabetes and reduce the risk of misdiagnosis and subsequent overtreatment of diabetes in elderly patients.
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http://dx.doi.org/10.1186/s12902-019-0338-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371438PMC
February 2019

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Am J Hum Genet 2019 01 27;104(1):112-138. Epub 2018 Dec 27.

School of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
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http://dx.doi.org/10.1016/j.ajhg.2018.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323610PMC
January 2019

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Nat Commun 2018 10 26;9(1):4455. Epub 2018 Oct 26.

Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
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http://dx.doi.org/10.1038/s41467-018-06356-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203810PMC
October 2018

Impact of Glucose Measuring Systems and Sample Type on Diagnosis Rates of Diabetes Mellitus.

Diabetes Ther 2018 Oct 5;9(5):2029-2041. Epub 2018 Sep 5.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Introduction: The use of glucose point-of-care testing (POCT) devices for the diagnosis of diabetes mellitus (DM) is an ongoing controversy. In patient management, glucose concentrations are determined by POCT and core laboratory glucose methods, and the values are commonly compared even though the samples collected are different, namely, capillary whole blood and venous plasma. In individual patients it is difficult to distinguish between factors that can influence the results, such as sample type and measuring procedure. In this study, glucose concentrations obtained using POCT and core laboratory instruments were assessed to duplicate typical scenarios experienced in healthcare. Corresponding diagnosis rates of impaired glucose tolerance (IGT) and DM based on fixed, method-independent cutoffs were compared.

Methods: Glucose concentration was measured by the 2-h oral glucose tolerance test (OGTT) in samples collected from an inpatient cohort and a cohort from the general population. Two POCT methods, namely, a handheld unit-use glucometer and a small bench-top analyzer with batch reagents, and two core laboratory procedures were used to measure glucose concentrations. The sample types were whole blood and plasma samples collected from venous and capillary blood. The glycated hemoglobin level in whole blood was also determined.

Results: A total of 231 subjects were included in the study. The 2-h OGTT glucose concentrations in the capillary whole blood samples showed a positive bias of 0.8 mmol/L compared to those obtained using core laboratory plasma glucose methods, leading to increased rates of diabetes diagnosis. This bias decreased to 0.2 mmol/L when venous blood was used in the tests. A change in the method used by the core laboratory introduced a negative bias of 0.5 mmol/L and, consequently, a lower diagnosis rates.

Discussion And Conclusion: Venous blood samples measured at the point-of-care are the most suitable sample type for the measurement of the glucose concentration in the 2-h OGTT. The investigated unit-use POCT method is suitable for the diagnosis of IGT and DM when venous blood samples are collected. Importantly, changes in measurement procedures can introduce a bias and affect diagnosis rates, thereby emphasizing the need for further harmonization of glucose methods. A plain language summary is available for this article.
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http://dx.doi.org/10.1007/s13300-018-0495-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167283PMC
October 2018

Auricular acupuncture for treatment of preoperative anxiety in patients scheduled for ambulatory gynaecological surgery: a prospective controlled investigation with a non-randomised arm.

Acupunct Med 2018 08 9;36(4):222-227. Epub 2018 Jul 9.

Department of Anaesthesiology, University Medicine of Greifswald, Greifswald, Germany.

Objective: Auricular acupuncture (AA) is a promising alternative treatment for situational anxiety. The aim of this pilot investigation was to test the acceptability and feasibility of AA as a treatment for preoperative anxiety (PA) in preparation for a subsequent randomised controlled trial.

Methods: AA was offered for treatment of PA to female patients who were scheduled for ambulatory gynaecological surgery. In patients who agreed, indwelling fixed needles were applied bilaterally at the points MA-IC1, MA-TF1, MA-SC, MA-AH7 and MA-T the day before surgery. Patients who declined AA but agreed to be examined constituted the control group (no intervention). State anxiety (primary outcome) was measured using the State-Trait-Anxiety Inventory (STAI) before AA (time I), the evening before surgery (time II) and immediately before surgery (time III). Anxiety was measured with a 100 mm visual analogue scale (VAS-100); heart rate, blood pressure and serum cortisol were also quantified.

Results: Data from 62 patients (32 with AA and 30 with no intervention) were analysed. Whereas preoperative anxiety was reduced after AA the evening before surgery (P<0.01), anxiety levels in the control group increased from the first to the last measurement (P<0.001). Secondary outcomes were comparable between the patients from both groups.

Conclusions: AA was acceptable and feasible as a treatment for preoperative anxiety. The results were used for the sample size calculation of a subsequent randomised controlled clinical trial.

Trial Registration Number: NCT02656966; Results.
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http://dx.doi.org/10.1136/acupmed-2017-011456DOI Listing
August 2018

Definition, Classification and Diagnosis of Diabetes Mellitus.

Exp Clin Endocrinol Diabetes 2018 Jul 5;126(7):406-410. Epub 2018 Jul 5.

Kommission für Labordiagnostik der Diabetologie der Deutschen Diabetes Gesellschaft (DDG) und der Deutschen Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL) (Commission for Laboratory Diagnostics in Diabetology of the German Diabetes Association (DDG) and the German Association for Clinical Chemistry and Laboratory Medicine).

Aim of recommendations like this one issued by the German Diabetes Association is to provide the GP and diabetologist and his team with information he needs for his daily practice. These recommendations are updated annually. They are written by a group of experts, but they are not evidence based guidelines. This specific recommendation for diabetes diagnosis briefly describes the diabetes types and the different options for diagnosis. Also the caveats and the practical procedure are presented.
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http://dx.doi.org/10.1055/a-0584-6223DOI Listing
July 2018

External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact.

Clin Chem Lab Med 2018 07;56(8):1238-1250

Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

Background: Determination of blood glucose concentration is one of the most important measurements in clinical chemistry worldwide. Analyzers in central laboratories (CL) and point-of-care tests (POCT) are both frequently used. In Germany, regular participation in external quality assessment (EQA) schemes is mandatory for laboratories performing glucose testing.

Methods: Glucose testing data from the two German EQAs "Reference Institute for Bioanalytics" (RfB) and "INSTAND - Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien" (Instand) were analyzed from 2012 to 2016. Multivariable odds ratios (OR) for the probability to reach a "good" result were calculated. Imprecision and bias were determined and clinical risk of measurement errors estimated.

Results: The device employed was the most important variable required for a "good" performance in all EQAs. Additional participation in an EQA for CL automated analyzers improved performance in POCT EQAs. The reciprocal effect was less pronounced. New participants performed worse than experienced participants especially in CL EQAs. Imprecision was generally smaller for CL, but some POCT devices reached a comparable performance. Large lot-to-lot differences occurred in over 10% of analyzed cases. We propose the "bias budget" as a new metric to express the maximum allowable bias that still carries acceptable medical risk. Bias budgets were smallest and clinical risks of errors greatest in the low range of measurement 60-115 mg/dL (3.3-6.4 mmol/L) for most devices.

Conclusions: EQAs help to maintain high analytical performances. They generate important data that serve as the foundation for learning and improvement in the laboratory healthcare system.
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http://dx.doi.org/10.1515/cclm-2017-1142DOI Listing
July 2018

High-Sensitivity Cardiac Troponin T: Association of Creatine Kinase Catalytic Activity With the 99 Percentile.

Clin Chem 2018 06 13;64(6):973-974. Epub 2018 Apr 13.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany

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http://dx.doi.org/10.1373/clinchem.2017.285775DOI Listing
June 2018

Comprehensive Metabolic Profiling Reveals a Lipid-Rich Fingerprint of Free Thyroxine Far Beyond Classic Parameters.

J Clin Endocrinol Metab 2018 05;103(5):2050-2060

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Objective: Thyroid hormones are ubiquitously involved in human metabolism. However, the precise molecular patterns associated with alterations in thyroid hormones levels remain to be explored in detail. A number of recent studies took great advantage of metabolomics profiling to outline the metabolic actions of thyroid hormones in humans.

Methods: Among 952 participants in the Study of Health in Pomerania, data on serum free thyroxine (FT4) and thyrotropin and comprehensive nontargeted metabolomics data from plasma and urine samples were available. Linear regression analyses were performed to assess the association between FT4 or thyrotropin and metabolite levels.

Results And Conclusion: After accounting for major confounders, 106 of 613 plasma metabolites were significantly associated with FT4. The associations in urine were minor (12 of 587). Most of the plasma metabolites consisted of lipid species, and subsequent analysis of highly resolved lipoprotein subclasses measured by proton nuclear magnetic resonance spectroscopy revealed a consistent decrease in several of these species (e.g., phospholipids) and large low-density lipoprotein and small high-density lipoprotein particles. The latter was unique to men. Several polyunsaturated and saturated fatty acids displayed an association with FT4 in women only. A random forest-based variable selection approach using phenotypic characteristics revealed higher alcohol intake in men and an adverse thyroid state and menopause in women as the putative mediating factors. In general, our observations have confirmed the lipolytic and lipogenic effect of thyroid hormones even in the physiological range and revealed different phenotypic characteristics (e.g., lifestyle differences) as possible confounders for sex-specific findings.
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http://dx.doi.org/10.1210/jc.2018-00183DOI Listing
May 2018

Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes.

Clin Chem Lab Med 2018 07;56(8):1251-1258

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Background: Measuring the glucose concentration in whole blood samples is critical due to unsatisfactory glycolysis inhibition. Previous studies showed that Terumo tubes were superior, but they were taken off the European market in 2016 and alternatives were required. This initiated the present evaluation of glucose stability in five available tube types.

Methods: Venous blood samples were collected from 61 healthy volunteers to test tubes supplied by Terumo (two sets), Greiner FC-Mix, BD FX-Mixture and BD serum. After sampling, the contents were thoroughly mixed and centrifuged within an hour. The glucose concentrations were determined and the samples resuspended except for BD serum tubes (gel barrier). The first 30 samples were stored at room temperature and the remaining 31 at 4°C. After 24, 48, 72 and 96 h, all tubes were (re)centrifuged, and glucose concentration measurements were repeated.

Results: Changes in glucose concentrations over time differed significantly between the investigated tube types and to a certain extent between the two storing conditions. Glycolysis was most evident in the BD FX-mixture tubes. Good glucose stability was observed in samples retrieved form BD serum and Greiner tubes. The stability in both Terumo tubes was comparable to that in other studies. Although Greiner and both Terumo tubes are supposed to contain the same glycolysis inhibitor, glucose stability differed between these tubes.

Conclusions: We showed that Greiner is an acceptable alternative to Terumo and that glucose in serum that was rapidly separated from corpuscles by a gel barrier is stable for an extended time.
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http://dx.doi.org/10.1515/cclm-2017-0860DOI Listing
July 2018

Diagnostic performance of point-of-care and central laboratory cardiac troponin assays in an emergency department.

PLoS One 2017 28;12(11):e0188706. Epub 2017 Nov 28.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

Early diagnosis of myocardial infarction (MI) with cardiac troponin (cTn) assays at the point-of-care (POC) is suggested to shorten turn-around-time in the emergency department (ED). The present study aimed at comparing the diagnostic performance of two POC cTn assays with that of a central laboratory high-sensitivity (hs) method, under routine ED conditions. In 2,163 non-selected ED patients suspected for MI, the diagnostic performance of the POC troponin I (TnI), troponin T (TnT), and hs-TnT assay for the prediction of MI was evaluated based on receiver operating characteristic (ROC) analyses and compared with the performance based on the manufacturers' cut-offs. Due to an observed association between renal function as determined by estimated glomerular filtration rate (eGFR) and cTn concentrations, all analyses were stratified by renal function. In patients with normal renal function (eGFR > 60 mL/min/1.73m2), POC and hs assays showed a comparable diagnostic performance as quantified by the area under the ROC curve (AUC) of about 0.88. The ROC-derived optimal cut-off (OCO) levels for the different cTn assays clearly changed with decreasing kidney function. Impaired kidney function required OCO to be three to five times higher to achieve a comparable performance. Particularly cTnT concentrations were strongly associated with renal function. The three cTn assays demonstrated equivalent diagnostic performance in ED-patients admitted with suspected ACS in relation to the release diagnosis, supporting the use of POC testing in this setting. The present results implicate that application of eGFR-specific OCOs may decrease false-positives among patients with impaired renal function. Providing individual cut-offs depending on patients' eGFR might be an appropriate add-on tool to improve specificity in the diagnosis of MI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705122PMC
December 2017

Periodontitis and Non-alcoholic Fatty Liver Disease, a population-based cohort investigation in the Study of Health in Pomerania.

J Clin Periodontol 2017 Nov 22;44(11):1077-1087. Epub 2017 Sep 22.

Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.

Background: Non-alcoholic fatty liver disease (NAFLD) affects 20%-30% of adults with risk factors like obesity and insulin resistance putatively acting through chronic low-grade inflammation. Because periodontitis elicits low-grade inflammation, we hypothesized that it could contribute to NAFLD occurrence.

Objective: To investigate epidemiologic associations between periodontitis and the incidence of NAFLD among 2,623 participants of the Study of Health in Pomerania.

Methods: Periodontitis at baseline was defined as the percentage of sites (0%, <30%, ≥30%) with (i) clinical attachment level (CAL) ≥3 mm; (ii) probing pocket depth (PD) ≥4 mm. Incident NAFLD was defined as a significant increase in liver echogenicity on ultrasound relative to the kidneys, with the diaphragm indistinct or the echogenic walls of the portal veins invisible.

Results: After a median 7.7 years of follow-up, 605 incident NAFLD cases occurred at a rate of 32.5 cases per 1,000 person-years. Relative to participants without CAL ≥3 mm, NAFLD incidence was elevated slightly in participants with <30% of sites affected and moderately in participants with ≥30% of sites affected (multivariable-adjusted incidence rate ratio = 1.28, 95% CI, 0.84, 1.95 and 1.60, 95% CI, 1.05-2.43), respectively. A similar dose-response relationship was not observed for PD.

Conclusion: History of periodontitis may be a risk factor for NAFLD.
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http://dx.doi.org/10.1111/jcpe.12800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650532PMC
November 2017

The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population.

Clin Biochem 2017 Dec 10;50(18):1198-1202. Epub 2017 Aug 10.

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address:

Objectives: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.

Design & Methods: CTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.

Results: The 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.

Conclusion: While the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.
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http://dx.doi.org/10.1016/j.clinbiochem.2017.08.006DOI Listing
December 2017

Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.

Circ Cardiovasc Genet 2017 Aug;10(4)

Background: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.

Methods And Results: We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (<5×10) novel loci and replicated a prior association with S We identified 3 loci at , , and that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.

Conclusions: We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.
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http://dx.doi.org/10.1161/CIRCGENETICS.116.001667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567993PMC
August 2017
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